Effects of peripheral or central GLP-1 receptor blockade on leptin-induced suppression of appetite.
Leptin and glucagon-like peptide-1 (GLP-1) were proved to act in concert to control the activity of feeding centres. Since leptin receptor was identified in the gut endocrine L cells and neurons producing GLP-1, we have checked whether GLP-1 mediates the effects of leptin on feeding and drinking behaviour. To this aim, an intraperitoneal or intracerebroventricular injection of exendin (9 - 39), a GLP-1 antagonist, (50 or 10 microg per rat, respectively) followed by leptin (100 or 5 microg per rat, respectively) was made and 24-hour food intake and body weight changes were measured. Previous injection of exendin (9-39) completely abolished the supressory effect of peripheral leptin on food intake and body weight gain. Moreover, exendin (9-39) significantly attenuated the effect of intracerebroventricular leptin on food but not water consumption. It is concluded that intact GLP-1 signalling is necessary to mediate the effect of leptin on food intake in the rat. Conversely, leptin seems to affect the thirst center function independently of GLP-1. Also, these findings produce further evidence for close interactions between long- and short-term factors regulating the activity of feeding centres.
Nowak
A
A
Department of Behavioral Pathophysiology, Institute of General and Experimental Pathology, Medical University of Lodz, Lodz, Poland.
Bojanowska
E
E
D000704:Analysis of Variance; D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects*; D000067757:Glucagon-Like Peptide-1 Receptor; D007276:Injections, Intraventricular; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D017933:Peripheral Nervous System / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018027:Receptors, Glucagon / Q000037:antagonists & inhibitors*
D001067:Appetite Depressants; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D020738:Leptin; D010446:Peptide Fragments; D018027:Receptors, Glucagon; C083773:exendin (9-39)